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Cystic fibrosis – characterization of the adult population in Portugal
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Raja, P.A. Flume" "autores" => array:2 [ 0 => array:2 [ "nombre" => "T.H." "apellidos" => "Raja" ] 1 => array:2 [ "nombre" => "P.A." "apellidos" => "Flume" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173511516300306?idApp=UINPBA00004E" "url" => "/21735115/0000002200000003/v1_201605310123/S2173511516300306/v1_201605310123/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Cystic fibrosis – characterization of the adult population in Portugal" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "141" "paginaFinal" => "145" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Silva, A. Amorim, P. Azevedo, C. Lopes, F. Gamboa" "autores" => array:5 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Silva" "email" => array:1 [ 0 => "ana2alves@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Amorim" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Azevedo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Lopes" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "F." "apellidos" => "Gamboa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Department of Respiratory Medicine, Centro Hospital e Universitário de Coimbra, Coimbra, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Respiratory Medicine, Centro Hospitalar de São João, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Respiratory Medicine, Centro Hospitalar de Lisboa Norte – Hospital de Santa Maria, Lisbon, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Chart 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1066 "Ancho" => 2466 "Tamanyo" => 98179 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Age at diagnosis.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cystic fibrosis (CF) is the most common autosomal recessive monogenic disease in the Caucasian population. Its incidence in Portugal is estimated at 1:8000 live births, based on preliminary results obtained from the neonatal screening pilot project, ongoing for two years. This pilot project encountered almost only F508del homozygous, therefore its true incidence is perhaps underestimated. However, precise statistical data does not exist. In all 28 European Union countries, the prevalence is estimated to be 0.74 per 10,000 individuals.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> The average life expectancy has been steadily increasing and CF is no longer an exclusively pediatric disease, affecting more adults than before. In the 1940s to 1960s CF was usually fatal in early childhood because of the consequences of recurrent pulmonary infection and malnutrition due to pancreatic failure and subsequent mal-digestion of nutrients. Initial improvements in care included the introduction of pancreatic enzyme replacement therapy in the 1960s and enteric coated enzymes in the early 1980s to treat pancreatic insufficiency in combination with a high calorie and high fat diet. Systemic antibiotic therapy for lung infection and the development and use of inhaled antibiotic therapies over successive decades have been important therapeutic developments. The introduction of mucolytics including dornase alpha, hypertonic saline and more effective methods of airway clearance have contributed to the major therapeutic advances from the 1970s to the current era. These and other supportive therapies for complications of CF have been delivered by multidisciplinary teams in CF centers. Centralized care with dedicated CF teams has become and remains the cornerstone of care delivery in CF.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a> According to the European Cystic Fibrosis Society patient registry (ECFSPR) data, the median predicted age of survival at 2010 was 43.5 years in UK.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> In Portugal there is no national data, however, according to CF adult follow-up patients in specialized centers, the average age is 30.7 years.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">3</span></a> In our country there are 300 follow-up patients in specialized CF outpatient clinics (less than expected considering the incidence in Portugal), and approximately one-third are adults. In this group, pulmonary disease tends to be more advanced and associated with several co-morbidities such as diabetes, metabolic bone disease, cancer, toxic effects and complications associated with lung transplantation.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">CF is caused by mutations in the long arm of chromosome 7, encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), which is expressed predominantly in the epithelial cells.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> So far more than 2000 mutations have been identified,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> the most common is F508del and the others are rare.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> Mutations in this gene cause changes in the transepithelial ion transport of chloride and the organ most affected is the lung, which is the greatest contributor to the morbimortality. It results in impaired mucociliary clearance and predisposition to airway infection.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">5</span></a> Surprisingly, infections are caused by a limited number of bacteria. In adults, <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> and <span class="elsevierStyleItalic">Staphylococcus aureus</span> are the most frequent microorganisms.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> Recent reports document an increasing incidence of new Gram-negative pathogens such as <span class="elsevierStyleItalic">Stenotrophomonas maltophilia, Alcaligenes xylosoxidans</span> and <span class="elsevierStyleItalic">Burkholderia cepacia complex</span>.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Even when aggressive treatment of the respiratory disease is employed, there is a progressive decline in lung function, with a moderate-severe impairment present in 60% of adults.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">10</span></a> When lung function is severely compromised lung transplantation may be indicated. In these patients, bilateral lung transplantation is the only option, given the chronic bronchial infection.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The disease is multisystemic and affects all organs that express CFTR, including not only lung but also pancreas, intestine, biliary tract, vas deferens, sweat and salivary glands.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Exocrine pancreatic insufficiency is present in 85% of patients with CF and the clinical manifestations (such as steatorrhoea and poor nutrition) are mostly dealt with by diet and pancreatic enzyme replacement. In some patients (8–15%), as time progresses, there is destruction of insulin-producing cells, resulting in endocrine pancreatic insufficiency, manifested by diabetes mellitus. Pancreatic sufficiency (15%) may be present at an older age and usually patients have milder lung disease and normal or borderline sweat electrolyte values.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Usually only a small percentage of patients (3–5%) have liver disease, which manifests clinically as neonatal jaundice, hepatic steatosis or biliary cirrhosis. It is also possible to observe a micro-gallbladder and increased incidence of gallstones (12% of patients), which normally does not cause any symptoms and does not require treatment.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Recurrent constipation and distal intestinal obstruction syndrome (previously known as meconium ileus equivalent) are features in older patients with CF.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Approximately 97% of males with CF are infertile due to azoospermia attributed to congenital bilateral absence of the vas deferens. Infertility may be the initial presentation for some males with mild disease. However, a male gender CF patient may have children, by puncturing the seminal vesicles, doing sperm collection and <span class="elsevierStyleItalic">in vitro</span> fertilization. In the female gender the ovulation is normal, but given the adverse conditions, there is a decrease in fertility due to anovulatory cycles. The presence of thick cervical mucus, which functions as a barrier to sperm, is another factor contributing to lower fertility.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Sweat glands in CF patients do not show any histological abnormalities but have pronounced abnormalities in sodium-chloride homeostasis due to defective CFTR function. The consequence of this defect is a resultant sweat with a relatively elevated concentration of chloride and sodium compared with normal sweat. This landmark discovery led to the development of the sweat test for diagnosis in 1959.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a> An increased concentration of electrolytes in the sweat may result in hyponatremic/hypochloremic dehydration secondary to salt depletion or hypokalemic metabolic alkalosis secondary to chronic salt loss. Once the diagnosis is known and regular salt replacement offered this problem is rarely seen.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Despite the technological advances in recent years, in terms of diagnostic and therapeutic approach, CF remains a progressive and lethal chronic disease.</p><p id="par0055" class="elsevierStylePara elsevierViewall">This study aims to characterize the Portuguese adult population diagnosed with CF followed in specialized centers during 2012.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="par0060" class="elsevierStylePara elsevierViewall">Retrospective analysis based on clinical data of adult CF follow-up patients in the three specialized centers in Portugal (<span class="elsevierStyleItalic">Centro Hospital e Universitário de Coimbra</span>, <span class="elsevierStyleItalic">Centro Hospitalar de São João</span>, Porto and <span class="elsevierStyleItalic">Centro Hospitalar de Lisboa Norte – Hospital de Santa Maria</span>, Lisbon, Portugal), where all of CF patients are seen, in 2012. The following variables were analyzed: geographical distribution, gender, age (December 31st, 2012), age at diagnosis, mutations/CFTR genotype, nutritional status, pancreatic function, ventilatory function (FEV<span class="elsevierStyleInf">1</span>), chronic bronchial infection, lung transplantation and mortality. The nutritional status was evaluated according to the <span class="elsevierStyleItalic">World Health Organization</span> and classified as underweight (BMI<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>18.5<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), normal weight (BMI 18.5–24<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>), overweight (BMI 26–39<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>) and obesity (BMI<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>).<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a> The severity of lung disease was defined based on the forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV<span class="elsevierStyleInf">1</span>) and categorized as very severe (FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>20%), severe (FEV<span class="elsevierStyleInf">1</span> 21–40%) moderate (FEV<span class="elsevierStyleInf">1</span> 39–69%), mild (FEV<span class="elsevierStyleInf">1</span> 89–70%) and normal (FEV<span class="elsevierStyleInf">1</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>90). Chronic airway infection was considered if, in a period of six months, three or more positive cultures of the same bacteria were isolated. The reference ranges of sweat test by the conductivity (semi-quantitative) method are >90<span class="elsevierStyleHsp" style=""></span>mmol/L if positive for CF; 50–90<span class="elsevierStyleHsp" style=""></span>mmol/L borderline (could be CF); <49<span class="elsevierStyleHsp" style=""></span>mmol/L negative/normal.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Results</span><p id="par0065" class="elsevierStylePara elsevierViewall">In 2012, there were 89 adult follow-up patients with FQ were in Portugal, 42 at the Hospital de Santa Maria, in Lisbon, 24 at the Centro Hospitalar e Universitário de Coimbra-Hospitais da Universidade de Coimbra and 23 at the Centro Hospitalar de São João, in Porto. Of the 89 patients, 48 (54%) were female and 41 (46%) were male gender. The average age was 31.23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9 years (minimum of 19 and maximum of 58 years). The age distribution was mostly between 23 and 27 years (<a class="elsevierStyleCrossRef" href="#fig0005">Chart 1</a>). The age at diagnosis ranged from two months to 58 years, with a median age of 13 years, and 34 (38%) were diagnosed in adulthood (<a class="elsevierStyleCrossRef" href="#fig0010">Chart 2</a>). The sweat test was positive in 85 (94%) patients, borderline in four (5%) and negative in one patient (1%). The genetic study of the CFTR locus was done for all patients. The most frequent mutation was F508del in 95 patients (54.9%), 27 patients (30%) were homozygotes and 41 (46%) heterozygous for this mutation. The second most frequent mutation was R334W, identified in 22 patients (12.7%). The different genotypes and their frequency are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Of the 89 patients, 49 (56%) had pancreatic insufficiency and 7 (9%) were diabetic. Regarding nutritional status, mean body mass index (BMI) was 20.93<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.05<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, of which 24 (27.3%) were underweight, 54 (61.4%) normal weight, 8 (9.1%) overweight and 2 (2.3%) obese. Of the 77 patients (excluding patients transplanted up to 2011), 3 (3.9%) had very severe ventilatory function, 15 (19.48%) severe, 31 (40.26%) moderate, 16 (20.78%) mild and 12 (15.58%) patients had normal ventilatory function. The average FEV<span class="elsevierStyleInf">1</span> value was 62.75<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>27.84%, with a minimum of 10.50% and a maximum of 133.90%. Considering all 77 patients, only one (1.3%) did not have chronic airway infection. Of the patients with chronic infection, 31 (40.3%) had only one microorganism isolated and 45 (58.4%) had more than two microorganisms. The most common microorganism was methicillin-sensitive <span class="elsevierStyleItalic">S. aureus</span> in 49 patients and <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> in 41 patients. The frequency of microorganisms identified is shown in <a class="elsevierStyleCrossRef" href="#fig0015">Chart 3</a>. Of the patients undergoing lung transplantation (17%), 7 were female and 8 male gender. The average survival time after lung transplantation was 3.53<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.88 years, with a minimum of one year and a maximum of eight years. During 2012 two female patients (2.2%) died at 21 and 36 years, due to lung transplant rejection and sepsis with pulmonary origin, respectively.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">This study is the first description of the Portuguese adult CF population, which is particularly important, since it gives a better understanding of the real situation. The average age of CF patients in our population (31.23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9 years) reflects the increased survival in this pathology, with a significant percentage of patients diagnosed in adulthood (38%).<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">13</span></a> Newborn screening for CF started as a pilot project in Portugal in 2013 and will continue until the end of 2015. This screening when implemented in other European countries seems to prevent early CF-related deaths and leads to a substantial and prolonged health gain for patients with CF.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> This study highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical manifestations. The wide heterogeneity of mutations found in these patients complies with that described in South Europe.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">14</span></a> Good nutritional status and reasonable ventilatory function reflect not only a wide spectrum of clinical severity, as well as a more efficient treatment regime and very regular follow up, based on international recommendations. Therefore, specialized follow up is of utmost importance.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Lung transplantation is, increasingly, assumed to be a therapeutic alternative in the later stages of CF, and these patients have a better prognosis if they have this intervention.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Protection of human and animal subjects</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Confidentiality of data</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Right to privacy and informed consent</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres669191" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Discussion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec675623" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 4 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 6 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-10-05" "fechaAceptado" => "2015-12-22" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec675623" "palabras" => array:3 [ 0 => "Cystic fibrosis" 1 => "F508del" 2 => "Adulthood" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The incidence of cystic fibrosis (CF) in Portugal is estimated at 1:8000 live births, although there is a lack of accurate statistics. The average life expectancy has been steadily increasing and CF is no longer an exclusively pediatric disease.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Characterize the Portuguese adult population with the diagnosis of CF.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Retrospective study based on clinical data of adult CF follow-up patients in the three specialized centers in Portugal where all of CF patients are seen, during 2012.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In 2012, there were 89 follow-up patients, 48 (54%) female and 15 (17%) lung transplanted. The average age was 31.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>9 years. The median age at diagnosis was 13 years and 34 (38%) were diagnosed in adulthood. The most frequent mutation was F508del (54.9%). Of the 89 patients, 49 patients (56%) had pancreatic insufficiency, 7 (9%) were diabetic and 42 patients (47.7%) had a body mass index (BMI) <20<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>. As to ventilatory function, the average value of the forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s (FEV<span class="elsevierStyleInf">1</span>) was 58.45<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>28.59%. Only one of 77 patients did not have chronic airway infection. The most commonly isolated germ was methicillin-sensitive <span class="elsevierStyleItalic">Staphylococcus aureus</span> in 49 patients (55%). During 2012, two patients (2.2%) died at the ages of 21 and 36 years.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Discussion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">This study is the first description of the Portuguese adult CF population, which is particularly important since it can give us a better understanding of the real situation. A significant percentage of these patients were diagnosed in adulthood, which highlights the need for diagnostic suspicion in a patient with chronic lung disease and atypical manifestations.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objectives" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Discussion" ] ] ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Chart 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 805 "Ancho" => 1647 "Tamanyo" => 65114 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Age distribution.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Chart 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1066 "Ancho" => 2466 "Tamanyo" => 98179 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Age at diagnosis.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Chart 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1478 "Ancho" => 2581 "Tamanyo" => 152168 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Airway microorganisms frequency.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">NMI: No mutation identified.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/F508del \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/del561E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/R334W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/G542X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/P205S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/I148N+IVS8-6(5T) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/3272-26 A-G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/<span class="elsevierStyleItalic">I234W</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/G85E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/R1066C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/3272-26A>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/R334W/R1177E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/IVS85T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/V232D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/L967S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/2183 AA-G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/R117H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F508del/NMI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/3272/26 A-G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Other heterozygous \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/A561E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1095471.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Genotype frequency.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patient Registry 2013 Annual Data Report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 6 | 14 |
| 2024 October | 40 | 40 | 80 |
| 2024 September | 36 | 20 | 56 |
| 2024 August | 64 | 31 | 95 |
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| 2024 June | 54 | 29 | 83 |
| 2024 May | 54 | 43 | 97 |
| 2024 April | 66 | 30 | 96 |
| 2024 March | 53 | 23 | 76 |
| 2024 February | 39 | 24 | 63 |
| 2024 January | 31 | 24 | 55 |
| 2023 December | 27 | 29 | 56 |
| 2023 November | 33 | 47 | 80 |
| 2023 October | 18 | 50 | 68 |
| 2023 September | 29 | 32 | 61 |
| 2023 August | 26 | 23 | 49 |
| 2023 July | 25 | 28 | 53 |
| 2023 June | 40 | 17 | 57 |
| 2023 May | 48 | 26 | 74 |
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